The research described in this proposal can be segmented into four distinct parts. These include: (a) the development of two complementary synthetic protocols which permit the stereoselective construction of a wide variety of 2'-deoxyribose and 2',3'- dideoxyribose derivatives of nucleotides from inexpensive, non- carbohydrate precursors; (b) the development of a synthetic protocol which permits the rapid, stereoselective construction of oxetane nucleosides from inexpensive, non-carbohydrate precursors; (c) the demonstration of the viability of this research by utilizing these synthetic protocols to prepare a number of nucleosides which exhibit significant anti-HIV activity; (d) the preparation of novel nucleoside analogues which may exhibit significant anti-HIV activity.